Per- and poly-fluoroalkyl substances (PFAS) are a group of fluorinated substances that are in the focus of researchers and regulators due to widespread presence in the environment and biota, including humans, of perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA). Fluoropolymers, high molecular weight polymers within the PFAS group, have unique properties that constitute a distinct class within the PFAS group. Fluoropolymers have thermal, chemical, photochemical, hydrolytic, oxidative and biological stability. They have negligible residual monomer and oligomer content and low to no leachables. Fluoropolymers are practically insoluble in water and not subject to long-range transport. With a molecular weight well over 100,000 Da, fluoropolymers cannot cross the cell membrane. Fluoropolymers are not bioavailable or bioaccumulative, as evidenced by toxicology studies on PTFE: acute and subchronic systemic toxicity, irritation, sensitization, local toxicity on implantation, cytotoxicity, in vitro and in vivo genotoxicity, hemolysis, complement activation, and thrombogenicity. Clinical studies of patients receiving permanently implanted PTFE cardiovascular medical devices demonstrate no chronic toxicity or carcinogenicity, reproductive or developmental or endocrine toxicity. This paper brings together fluoropolymer toxicity data, human clinical data, and physical-chemical-thermal-biological data for review and assessment to show that fluoropolymers satisfy widely accepted assessment criteria to be considered as "Polymers of Low Concern". This review concludes that fluoropolymers are distinctly different from other polymeric and non-polymeric per- and poly-fluoroalkyl substances and should be separated from them for hazard assessment or regulatory purposes. Grouping fluoropolymers with all classes of PFAS for "read across" or structure activity relationship assessment is not scientifically appropriate.